Evaluation of metabolic dysfunction-associated steatotic liver disease (MASLD) terminology in different clinical settings
Authors: Paula Iruzubieta, Alvaro Santos-Laso, María Teresa Arias-Loste, José Luis Calleja, Javier Crespo
Journal: Journal of Hepatology (2023)

The nomenclature of non-alcoholic fatty liver disease (NAFLD) has recently been replaced by consensus.[1]Rinella M.E. Lazarus J.V. Ratziu V. et al.A multi-society Delphi consensus statement on new fatty liver disease nomenclature.J Hepatol. June 2023; https://doi.org/10.1016/J.JHEP.2023.06.003Abstract Full Text Full Text PDF Google Scholar A detailed Delphi process concluded that the overarching term "steatotic liver disease (SLD)" and, more specifically, the term "metabolic dysfunction-associated steatotic liver disease (MASLD)" provide an affirmative non-stigmatising definition of this metabolic disorder. Steatosis with at least one of five cardiovascular risk factors is a prerequisite for a correct diagnosis. Interestingly, the umbrella term SLD encompasses different subtypes based on the main disease driver.[1]Rinella M.E. Lazarus J.V. Ratziu V. et al.A multi-society Delphi consensus statement on new fatty liver disease nomenclature.J Hepatol. June 2023; https://doi.org/10.1016/J.JHEP.2023.06.003Abstract Full Text Full Text PDF Google Scholar Recent data showed minimal discrepancies between MASLD and NAFLD;[2]Song S.J. Lai J.C.-T. Wong G.L.-H. et al.Can we use old NAFLD data under the new MASLD definition?.J Hepatol. August 2023; https://doi.org/10.1016/J.JHEP.2023.07.021Abstract Full Text Full Text PDF Google Scholar,[3]Perazzo H. Pacheco A.G. Griep R.H. et al.Changing from NAFLD trough MAFLD to MASLD: similar prevalence and risk factors in a large Brazilian cohort.J Hepatol. September 2023; https://doi.org/10.1016/J.JHEP.2023.08.025Abstract Full Text Full Text PDF PubMed Google Scholar however, the diagnostic robustness of this novel terminology must be tested in different populations and clinical settings. Furthermore, other diseases might cause hepatic steatosis, including chronic inflammatory diseases, which are not specifically considered in the classification by subtypes of SLD. Therefore, we performed an analysis of collected clinical and liver injury data to compare the NAFLD and MASLD criteria, and to address the impact of SLD subtype classification in patients from different healthcare settings, including those with immune-mediated inflammatory diseases (IMIDs). This multicentre cross-sectional study included data from two large prospective Spanish cohorts: a population-based cohort (ETHON cohort; n = 5,210) and an IMID cohort (n = 1,582). The ETHON cohort comprised participants from the general population aged 20-79 years, who were selected from primary care centres in Madrid, Santander and Valencia between 2015-2017.[4]Crespo J. Cuadrado A. Perelló C. et al.Epidemiology of hepatitis C virus infection in a country with universal access to direct-acting antiviral agents: data for designing a cost-effective elimination policy in Spain.J Viral Hepat. 2020; 27: 360-370https://doi.org/10.1111/jvh.13238Crossref PubMed Scopus (31) Google Scholar The IMID cohort (NCT03760172) included patients with inflammatory bowel disease, psoriasis, hidradenitis suppurativa and/or spondylarthritis who attended the Valdecilla University Hospital (Santander) or Puerta de Hierro University Hospital (Madrid) between 2018-2019. All participants were assessed by clinical evaluation, laboratory test and transient elastography. A controlled attenuation parameter ≥275 dB/m was considered as SLD, while significant fibrosis was defined by a liver stiffness measurement ≥8.0 kPa on transient elastography. NAFLD was defined as the presence of SLD in the absence of excessive alcohol consumption or other chronic liver disease. MASLD and other subtypes of SLD, such as MetALD, alcohol-related liver disease (ALD) and cryptogenic/specific aetiology SLD, were defined by the new statement.[1]Rinella M.E. Lazarus J.V. Ratziu V. et al.A multi-society Delphi consensus statement on new fatty liver disease nomenclature.J Hepatol. June 2023; https://doi.org/10.1016/J.JHEP.2023.06.003Abstract Full Text Full Text PDF Google Scholar Participants were excluded if they did not have a valid transient elastography measure or if other data were missing. The prevalence of SLD was 34.6% (95% CI 33.3-35.9%) and 33.1% (95% CI 30.7-35.4%) in the ETHON and IMID cohorts, respectively. Similar prevalence between NAFLD and MASLD criteria was observed in both cohorts (ETHON: 30.3% vs. 29.4%; IMID: 17.5% vs. 17.9%), and no significant differences were found in clinical, laboratory or liver injury data (Table S1). Indeed, the same proportion of patients with significant fibrosis was detected between NAFLD and MASLD in both cohorts. Among patients with SLD, the MASLD subtype was the most common in the ETHON cohort (n = 1,532; 85.0%) and the IMID cohort (n = 283; 54.1%). The second most frequent SLD subtype was ALD (n = 113; 6.3%) in the ETHON cohort, while it was the specific aetiology SLD subtype (n = 148; 28.3%) in the IMID cohort (4 patients with HCV infection and 144 with drug-induced liver injury). Regarding significant fibrosis, ALD subtype and specific aetiology SLD showed the highest proportion in both cohorts (Fig. 1). Notably, most patients in these two SLD subtypes had some cardiovascular factor that defines MASLD. Although significant fibrosis was more frequent among patients with MetALD than MASLD, no significant difference was reached in either of the two cohorts. Interestingly, the proportion of significant fibrosis for each SLD subtype from the IMID cohort was higher compared to the corresponding SLD subtype from the ETHON cohort (Fig. 1). Our findings showed a complete overlap between patients with NAFLD and MASLD in terms of metabolic comorbidities and degree of liver injury in both study cohorts. The ETHON cohort represents a typical primary care setting, and the IMID cohort typifies a specialized care scenario. This similarity between NAFLD and MASLD avoids the risk that the metabolic dysfunction-associated fatty liver disease nomenclature presented of not identifying patients with clinically relevant fatty liver disease.[5]Ayada I. van Kleef L.A. Alferink L.J.M. et al.Systematically comparing epidemiological and clinical features of MAFLD and NAFLD by meta-analysis: focusing on the non-overlap groups.Liver Int. 2022; 42: 277-287https://doi.org/10.1111/LIV.15139Crossref PubMed Scopus (0) Google Scholar Moreover, this correspondence will allow us to extrapolate the existing knowledge on pathogenesis and the results of different clinical trials of NAFLD to patients with MASLD. Furthermore, our findings reinforced the existing data on the interplay between metabolic factors and alcohol consumption in liver injury.[6]Odriozola A. Santos-Laso A. del Barrio M. et al.Fatty liver disease, metabolism and alcohol interplay: a comprehensive review.Int J Mol Sci. 2023; : 24https://doi.org/10.3390/IJMS24097791Crossref PubMed Google Scholar Herein, the new term MetALD recognizes the substantial overlap and synergy of alcohol consumption and metabolic factors on the pathogenesis of liver disease, justifying additional research in this subgroup of patients. Additionally, the increased prevalence of significant fibrosis among SLD patients with IMID compared to individuals within the general population is consistent with other studies that revealed an elevated prevalence of liver fibrosis in patients with IMID, even independently of the influence of classic metabolic risk factors.7Yongpisarn T. Namasondhi A. Iamsumang W. et al.Liver fibrosis prevalence and risk factors in patients with psoriasis: a systematic review and meta-analysis.Front Med. 2022; 9https://doi.org/10.3389/FMED.2022.1068157Crossref Google Scholar, 8Rodriguez-Duque J.C. Calleja J.L. Iruzubieta P. et al.Increased risk of MAFLD and liver fibrosis in inflammatory bowel disease independent of classic metabolic risk factors.Clin Gastroenterol Hepatol. 2022; https://doi.org/10.1016/J.CGH.2022.01.039Abstract Full Text Full Text PDF PubMed Google Scholar, 9Bessissow T. Le N.H. Rollet K. et al.Incidence and predictors of nonalcoholic fatty liver disease by serum biomarkers in patients with inflammatory bowel disease.Inflamm Bowel Dis. 2016; 22: 1937-1944https://doi.org/10.1097/MIB.0000000000000832Crossref PubMed Scopus (75) Google Scholar The pathogenesis influencing the co-existence of SLD and liver fibrosis related to IMIDs is poorly understood, but may involve metabolic syndrome, microbial dysbiosis, immune activation and drugs.[9]Bessissow T. Le N.H. Rollet K. et al.Incidence and predictors of nonalcoholic fatty liver disease by serum biomarkers in patients with inflammatory bowel disease.Inflamm Bowel Dis. 2016; 22: 1937-1944https://doi.org/10.1097/MIB.0000000000000832Crossref PubMed Scopus (75) Google Scholar Given the increased risk of developing liver steatosis and fibrosis demonstrated among patients with IMID, immune dysfunction is a factor that should be considered for the correct characterization of SLD. Spanish Carlos III Health Institute (ISCIII) [J. Crespo (FIS PI15/02138, PIE15/00079 and PI18/01304) and A. Santos-Laso (Sara Borrell Fellowship CD21/00039)]; Merck Sharp and Dohme (MISP IIS#52863). The authors have no potential conflicts (financial, professional, or personal) that are relevant to the manuscript. Please refer to the accompanying ICMJE disclosure forms for further details. Study design: PI, ASL, JC. Data acquisition: PI, MTAL, JLC. Analysis and interpretation of data: PI, ASL, JC. Drafting of the manuscript: PI, ASL. Critical review of the manuscript: All authors. Supervision: JC. All authors revised and approved the final version of the manuscript. The following are the supplementary data to this article: Download .pdf (.48 MB) Help with pdf files Multimedia component 1